DESCRIPTION: Ca2+/calmodulin-sensitive adenylyl cyclases (AC) are likely to be important for various types of synaptic plasticity. Transgenic mice deficient for type 1 adenylyl cyclase (I-AC) are deficient in certain types of spatial learning. Biochemical analysis of these mice indicate that the brain may contain at least one other Ca2+/calmodulin-sensitive AC. The long-term goals of this proposal are to determine if Ca2+/calmodulin-dependent ACs are required for LTP or spatial learning, determine which genes are in cultured primary neurons are regulated by cAMP, and determine if the Ca2+/calmodulin- sensitive ACs contribute to Ca2+ regulation of gene expression in cultured neurons. The sensitivity of IX-AC to CaM and Ca2+ will also be investigated. The specific aims of this project include the determination of the necessity of I-AC, III-AC and VIII-AC for specific forms of LTP or LTD and determining if the Ca2+/CaM sensitivity of I-AC is crucial for LTP and/or spatial learning. Furthermore, the investigator proposes to isolate the clone for IX-AC, determine if AC activity in neurons is regulated by membrane potential, determine what genes in cultured hippocampal neurons are regulated by cAMP, determine which forms of LTP activate CRE-mediated transcription, and determine if Ca2+/calmodulin-sensitive ACs contribute to regulation of gene expression in cultured neurons.